An important aspect for wound care is the control of infection, which may facilitate the healing process. Wound dressings are one of the most commonly used tools to protect the wound from infection. Antimicrobial agents are often incorporated into the wound dressing to treat and prevent infection. However, there are several disadvantages associated with use of antimicrobial agents. It has been observed that an increasing number of pathogens have developed resistance to the conventional antibiotic treatment. According to statistics, antibiotic-resistant pathogens are the primary reason for a majority of all lethal nosocomial infections. See Robson et al., Surg. Clin. N. Am. 77, 637-650 (1977). Furthermore, many antiseptic agents not only kill pathogens, but also impose a threat to the proliferating granulation tissue, fibroblasts and keratinocytes that may help with the wound healing process. Additionally, some antimicrobial agents may cause allergic reactions in some patients.
It is known that nitric oxide possesses a broad-spectrum of antimicrobial activity and may be used as an alternative to conventional antibiotics for drug resistant bacteria. Furthermore, some recent studies have demonstrated that nitric oxide may also play an important role in the wound healing process by promoting angiogenesis through stimulation of vascular endothelial growth factor (VEGF) and increased fibroblast collagen synthesis. See Schaffer M R, et al., Diabetes-impaired healing and reduced wound nitric oxide synthesis: A possible pathophysiologic correlation. Surgery 1997; 121(5):513-9; and Shi H P, et al., The role of iNOS in wound healing. Surgery 2001; 130 (2):225-9. Thus, nitric oxide presents a promising addition and/or alternative to the conventional antibiotic treatment for wound care.
Nitric oxide is a gas at ambient temperature and atmospheric pressure, and it has a short half-life in a physiological milieu. Several small molecule nitric oxide donor prodrugs have been developed which have contributed greatly to the understanding of nitric oxide in a number of disease states. However, due to issues with stability, indiscriminate NO-release, monotypical nitric oxide release kinetics, and inability to target specific tissue types no clinically viable solutions currently exist for administering nitric oxide outside of its gaseous form. Reproducibly delivering a the appropriate levels of nitric oxide for a given therapeutic indication is important because release of large amounts of nitric oxide may be toxic or create undesirable side effects such as decreases in angiogenesis or increased inflammation. Therefore, it has been challenging to use nitric oxide in the wound care field, other than via exogenous application, particularly in topical wound healing applications wherein nitric oxide has concentration dependent effects and benefits from delivery in a controlled and targeted manner.
Thus, the need exists for wound treatments and dressings that can release nitric oxide by a controlled delivery method.